Development of anti-citrullinated protein antibody and rheumatoid factor isotypes prior to the onset of rheumatoid arthritis

IgM ACPA 6 (20) 11 (37) 13 (43) Introduction We and others have previously shown that the development of rheumatoid arthritis (RA) is preceded by IgG anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) [1,2]. Furthermore, it was shown that other isotypes of ACPA (IgA and, to a lesser extent, the IgM isotype) also predate the onset of RA [3]. Moreover, smoking has been linked to the development of IgA ACPA in the preclinical phase [3]. We have extended these observations by using a previously described RA cohort in which serial preclinical serum samples were available [2]. Three sequential serum samples from 30 IgG ACPA-positive RA patients who had donated blood before disease onset were selected and were tested for IgM, IgA, and IgG isotypes of ACPA (using the anti-cyclic citrullinated peptide 2 test) and RF, as described previously, by using the ImmunoCap system (Phadia, Uppsala, Sweden) [3]. Smoking status (current or past smoker versus never smoked) was obtained retrospectively by chart review for 24 patients.